This K01 Career Development Award will provide Dr. Jennifer Sumner with the necessary skills to establish an independent research career focused on elucidating the psychological and biological mechanisms by which traumatic experiences contribute to cardiovascular disease (CVD) in women, the leading cause of death worldwide. Posttraumatic stress disorder (PTSD), the quintessential stress-related mental disorder, prospectively predicts increased CVD incidence. However, PTSD is a complex and heterogeneous disorder, and the aspects of PTSD that drive CVD risk are unknown. Mechanistic knowledge, particularly in women, is also lacking. These limitations impede the development of clinical applications to offset CVD risk. The overall aim of this K01 proposal is to begin to test a theoretically based biological model by which a core element of PTSD-posttraumatic fear responses (e.g., hypervigilance, re-experiencing)- relates to CVD and intermediate markers of cardiovascular health in women. Supported by a multidisciplinary team of expert mentors, Dr. Sumner will examine how posttraumatic fear responses (measured across self- report and psychophysiological levels of analysis) relate to cardiovascular health in women. The training plan will provide Dr. Sumner with required background and skills in several domains in order to become an independent investigator with an integrative research program on the mechanisms by which the psychological sequelae of trauma contribute to CVD in women. Through coursework, hands-on training, and mentored meetings, Dr. Sumner will address prior gaps in training and develop skills in 1) cardiovascular, neurological, and clinical epidemiology, 2) quantitative methods for analyzing epidemiologic and longitudinal data, 3) CVD- related physiology and biomarkers, and 4) psychophysiological measures of fear responses. The training plan also includes completion of a Master's of Science degree in Patient-Oriented Research from Columbia University. The proposed research program harnesses two richly characterized ongoing cohort studies to test how posttraumatic fear responses relate to cardiovascular risk in women. Using data from the Nurses' Health Study II (NHS II), a longitudinal epidemiologic study of women's health, Dr. Sumner will determine if self- reported posttraumatic fear symptoms relate to hypertension and CVD incidence and CVD-related biomarkers. In the REactions to Acute Care and Hospitalization (REACH) study, a study of risk for PTSD after acute coronary syndrome and its relation to recurrent cardiac events at New York-Presbyterian Hospital, Dr. Sumner will collect data to test associations between fear responses at multiple levels of analysis-self-report symptoms and psychophysiological indicators (i.e., skin conductance and heart rate)-with hospital readmission and cardiac event recurrence. These research and training activities will inform an R01 application that will comprehensively test the biological mechanisms by which posttraumatic fear symptoms across multiple levels of analysis contribute to CVD in women.